Subramaniam Sakthivel, Piñeyro Pablo, Derscheid Rachel J, Madson Darin M, Magstadt Drew R, Meng Xiang-Jin
Department of Biomedical Sciences & Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA 50011, USA.
Vet Immunol Immunopathol. 2017 Aug;190:18-25. doi: 10.1016/j.vetimm.2017.07.003. Epub 2017 Jul 10.
Porcine Reproductive and Respiratory Syndrome (PRRS) is an economically important swine viral disease worldwide. Current modified live-attenuated vaccines are ineffective against heterologous strains of PRRS virus (PRRSV) circulating in the field. In this study, we evaluated three dendritic cell (DC)-targeted vaccine candidates for their protective efficacy against heterologous PRRSV challenge. Ectodomain regions of DNA-shuffled structural proteins GP3, GP4, GP5 and M of PRRSV were fused together to form the vaccine antigen which was in turn fused with one of three recombinant antibodies each specific to a DC receptor: DC-SIGN, Langerin, and DEC205. The recombinant antibody-fused vaccine antigens were co-administered with polyinosinic-polycytidylic acid (poly (I:C)) adjuvant and subsequently challenged with a heterologous type 2 PRRSV strain (NADC20) in pigs. Our results demonstrate that pigs in DC-SIGN- and DEC205-targeted, but not Langerin- and non-targeted, vaccine groups showed significant IFN-γ- and IL-4-specific CD4T cell immune responses against the vaccine antigen in 7days post-challenge. Pigs in DC-SIGN- and Langerin-targeted vaccine groups showed greatly reduced IgG responses as compared to the DEC205- and non-targeted vaccine groups. The immune responses induced by DC-targeted vaccines did not reduce viremia and lung pathological lesions in type 2 PRRSV-challenged pigs. In contrast, pigs in Langerin-targeted vaccine group showed significantly increased serum viral titers and viral antigen in lung tissues at 7 and 14days post-challenge respectively. In conclusion, specific targeting of PRRSV antigen through DC-SIGN or DEC205 or Langerin-specific antibodies in the presence of poly (I:C) adjuvant induced immune responses that failed to protect pigs against heterologous type 2 PRRSV challenge.
猪繁殖与呼吸综合征（PRRS）是一种在全球范围内具有重要经济影响的猪病毒性疾病。目前的改良活疫苗对田间流行的PRRS病毒（PRRSV）异源毒株无效。在本研究中，我们评估了三种靶向树突状细胞（DC）的候选疫苗对异源PRRSV攻击的保护效果。将PRRSV的DNA改组结构蛋白GP3、GP4、GP5和M的胞外区域融合在一起形成疫苗抗原，该抗原再与三种分别针对DC受体（DC-SIGN、Langerin和DEC205）之一的重组抗体融合。将重组抗体融合的疫苗抗原与聚肌苷酸-聚胞苷酸（poly (I:C)）佐剂共同给药，随后用异源2型PRRSV毒株（NADC20）对猪进行攻击。我们的结果表明，在攻击后7天，靶向DC-SIGN和DEC205而非Langerin和非靶向的疫苗组中的猪，针对疫苗抗原表现出显著的IFN-γ和IL-4特异性CD4 T细胞免疫反应。与靶向DEC205和非靶向的疫苗组相比，靶向DC-SIGN和Langerin的疫苗组中的猪的IgG反应大大降低。靶向DC的疫苗诱导的免疫反应并未降低2型PRRSV攻击猪的病毒血症和肺部病理损伤。相反，靶向Langerin的疫苗组中的猪在攻击后7天和14天分别显示血清病毒滴度和肺组织中的病毒抗原显著增加。总之，在poly (I:C)佐剂存在下，通过DC-SIGN或DEC205或Langerin特异性抗体对PRRSV抗原进行特异性靶向诱导的免疫反应未能保护猪免受异源2型PRRSV攻击。
